Studies on the mechanisms of the host range determination of lentiviruses from carnivora

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Human immunodeficiency virus (HIV) belongs to the genus lentivirus and induces immunodeficiency in humans. Animals also have own lentiviruses and cause a variety of diseases. Cats also have a pathogenic lentivirus called feline immunodeficiency virus (FIV) and FIV induces immunodeficiency in rats similar to the HIV infection in humans. Large felids such as lions also have lentiviruses, however the viruses are non-pathogenic in natural hosts. To elucidate the mechanisms on the determination of the host range of the feline lentiviruses is important to cope with the emergence of the novel lentiviral infections in felids. We analyzed the mechanisms of FIV infection in a feline glial cell line termed G355-5 cells. FIV strain Petaluma (subtype A) infected the G355-5 cells irrespective of the expression of feline CD134 (fCD134), primary receptor for T-lymphotropic FIV. On the other hand, strain TM2 (subtype B) required the ectopic expression of fCD134 to infect the G355-5 cells. Intriguingly, the strong expression of offCD134 suppressed the infection by strain Petaluma in the G355-5 cells. In addition, the expression of fCD134 suppressed the efficient viral release of strain TM2 from the infected G855-5 cells. The strain TM2-infected G355-5 cells transduced with fCD134 (G355-5/fOX40 cells) became a state of persistent infection. At 50 days post-infection, the infected cells released the infectious FIV particles into the culture medium and the virus was designated as strain TM2PI. TM2PI infected naive G355-5 cells in the absence of fCD134, indicating that strain TM2 mutated in the G355-5 cells to be an fCD134-independent strain. Furthermore, the cells also became a state of persistent infection and can be maintained without coculturing with uninfected G355-5 cells. Because both virus and producer cells were not modified by the genetic engineering techniques, the producer cells may be suitable for antigen preparation of the virus for vaccines.